Multi-parametric MRI in Patients Suspected for Muscle Invasive Bladder Cancer: a New Local Staging Paradigm

• mpMRI plus a same-day cystoscopic bladder biopsy (Diagnostic test): mpMRI plus a same-day cystoscopic bladder biopsy
• TURBT (Procedure): Transurethral resection of the bladder tumor, blood withdrawal shortly before and after TURBT

Primary outcomes

• Progression free survival [2 years]: Progression-free survival, defined as the time between randomisation and one of the following events, whichever occurs first: * Diagnosis of distant metastases * Diagnosis of loco-regional nodal recurrence * Death from any cause

Secondary outcomes

• Time to definitive treatment [2 years]: Definitive treatment is defined as TURBT in case of NMIBC and radical cystectomy with or without neoadjuvant chemotherapy or chemoradiotherapy in case of MIBC. Time to definitive treatment is the time between randomisation and the first of these mentioned treatments.
• Health-related quality of life [2 years]: Generic health-related quality of life will be assessed at baseline, 6 months, 12 months and 24 months using the EuroQol 5 dimensions 5 levels (EuroQol 5D) questionnaire.
• Hospital-related healthcare costs [2 years]: Hospital registries will be used to identify all items / procedures / activities related to the management of the bladder cancer and obtain a valid and reliable estimate of the costs. Unit costs will be based on the Dutch manual for costing studies.
• Cost-effectiveness [2 years]: Unit costs will be based on the Dutch manual for costing studies. Effectiveness will be measured in terms of quality-adjusted life years (QALYs), following the Dutch guideline for economic evaluation (EuroQol 5D).
• Circulating tumor cells [Before (at least on same day) and after (max. 60 minutes) TURBT]: Percentage of patients with CTCs/CTC clusters in the blood sample post-TURBT, among those who were CTC-free pre-TURBT, analysed by blood withdrawal shortly before and after TURBT.
• Metastatic potential of CTC-positive samples [Before (at least on same day) and after (max. 60 minutes) TURBT]: Post-TURBT CTC-positive samples of patients that were CTC negative prior to TURBT will be further analyzed for the expression levels of bladder cancer metastasis-associated genes using principal component- and heatmap analysis.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patients (18+ years of age)
* Clinically suspected MIBC
* No lymph node or distant metastases
* Written informed consent

Exclusion Criteria:

* Unable or unwilling to undergo mpMRI
* Unfit for TURBT
* Unfit for definitive treatment with curative intent
* A history of cancer, including bladder cancer, except: non-melanoma skin cancer, prostate cancer on active surveillance or a solid malignant tumor ≥5 years disease-free since last treatment

• Results publication: van Koeverden SW, van Hoogstraten LM, de Rooij M, van der Leest M, Grutters JP; BladParadigm study group; Kiemeney LA, van der Heijden AG. Multiparametric MRI for local staging in patients with suspected muscle-invasive bladder cancer: study protocol for a multicentre, non-inferiority randomised controlled trial (the BladParadigm study). BMJ Open. 2025 Aug 16;15(8):e100002. doi: 10.1136/bmjopen-2025-100002. PMID 40819867

• A. G. van der Heijden, Dr., Principal investigator, Radboud University Medical Center